CAJ | 학술논문

目的了解福建省籍各地市人群地中海贫血(简称地贫)的基因携带率、基因突变类型及其分布特征.方法采用分层整群方法随机抽取福建省9地市籍贯体检人群的静脉血,测定红细胞参数和用高效液相色谱法分析血红蛋白,表型阳性的标本用单管多重PCR方法检测中国人常见的3种α缺失型突变和PCR-寡核苷酸探针反相斑点杂交法检测非缺失α地贫基因突变及β-地贫基因突变.未知突变采用DNA直接测序法进行分析.结果 11234人中,共检出α和β地贫504例,地贫总携带率为4.41％.其中356例样本为α地贫,--SEA/αα236例、-α3.7/αα 67例、-α4.2 /αα 24例、血红蛋白H病4例(-α3.7/--SEA3例,-α4.2/--SEA1例)、-α3.7/-α3.7 1例、-α3.7/-α4.21例、非缺失型α地贫中,ααQS/αα7例、ααCS/αα 3例、ααWS/αα 2例,最常见的为--SEA/αα占全部基因突变的66.29％;148例为β-地贫,共检出12种基因突变类型,IVS-2-654(C→T)65例、CD41-42(-TCTT)40例、CD17(A→T)12例、-28(A→G)10例、CD27-28 (+C)7例、起始密码子ATG→AGG 5例、CD26(G→ A)2例、CD71-72(+A)1例、IVS-1-1(G→T)1例、CD43(G→T)1例、-29(A→G)2例、Codon 36(-C)2例,其中最常见的是IVS-2-654(C-→T)和CD41-42(-TCTT),占全部基因突变的70.95％,并再次在中国人群中发现了Codon 36(-C)的新的突变类型.α地贫复合β地贫双重杂合子9例.结论阐明福建省籍各地市人群α和β地贫的基因突变类型和频率,在国内具有较高的地贫发生率和遗传异质性,该研究为在本地区开展遗传咨询和产前诊断提供了参考借鉴资料.
목적 료해복건성적각지시인군지중해빈혈(간칭지빈)적기인휴대솔、기인돌변류형급기분포특정.방법 채용분층정군방법수궤추취복건성9지시적관체검인군적정맥혈,측정홍세포삼수화용고효액상색보법분석혈홍단백,표형양성적표본용단관다중PCR방법검측중국인상견적3충α결실형돌변화PCR-과핵감산탐침반상반점잡교법검측비결실α지빈기인돌변급β-지빈기인돌변.미지돌변채용DNA직접측서법진행분석.결과 11234인중,공검출α화β지빈504례,지빈총휴대솔위4.41％.기중356례양본위α지빈,--SEA/αα236례、-α3.7/αα 67례、-α4.2 /αα 24례、혈홍단백H병4례(-α3.7/--SEA3례,-α4.2/--SEA1례)、-α3.7/-α3.7 1례、-α3.7/-α4.21례、비결실형α지빈중,ααQS/αα7례、ααCS/αα 3례、ααWS/αα 2례,최상견적위--SEA/αα점전부기인돌변적66.29％;148례위β-지빈,공검출12충기인돌변류형,IVS-2-654(C→T)65례、CD41-42(-TCTT)40례、CD17(A→T)12례、-28(A→G)10례、CD27-28 (+C)7례、기시밀마자ATG→AGG 5례、CD26(G→ A)2례、CD71-72(+A)1례、IVS-1-1(G→T)1례、CD43(G→T)1례、-29(A→G)2례、Codon 36(-C)2례,기중최상견적시IVS-2-654(C-→T)화CD41-42(-TCTT),점전부기인돌변적70.95％,병재차재중국인군중발현료Codon 36(-C)적신적돌변류형.α지빈복합β지빈쌍중잡합자9례.결론 천명복건성적각지시인군α화β지빈적기인돌변류형화빈솔,재국내구유교고적지빈발생솔화유전이질성,해연구위재본지구개전유전자순화산전진단제공료삼고차감자료.
[Abstract] Objective To investigate the gene prevalence and spectrum of α-and β-thalassemia in Fujian province.Methods A total of 11234 of neonatal cord blood samples were collected for a prevalence study of α and β-thalassemia.All subjects included in this study were registered in 9 cities of Fujian province.A complete blood count and high performance liquid chromatography (HPLC) were performed in all samples,with microcytosis (MCV≤79 f1 and MCH≤27 pg) or HPLC positive cases further studied by DNA analysis.α-and β-thalassemia were determined by using gap-PCR and reverse dot blot (RDB) assays.Unknown positive samples were analyzed directly with DNA sequencing.Results Of all 11234 cord blood samples,356 were identified as from α-thalassemia gene carriers,7 deletion genotypes were identified including 236 (--SEA/αα)cases,67 (-α3.7/αα) cases,24 (-α4.2/αα) cases,3 (-α3.7/--SEA) cases,1 (-α4.2/--SEA) cases,1 (-α3.7/-α3.7)cases,1 (-α3.7/-α4.2) cases; 3 non-deletion genotypes were detected,including 7 (ααQS/αα) cases,3 (ααCS/αα) cases,2 (ααWS/αα) cases,the most common mutation was--SEA/αα,which accounted for 66.29％,148 individuals were found to have β-hemoglobin gene mutations.12 different mutations were identified,namely 65 IVS-2-654 (C→ T) cases,40 CD41-42 (-TCTT),12 CD17 (A→ T) cases,10-28(A→G) cases,7 CD27-28(+C) cases,5 start codon ATG→AGG cases,2 CD26(G→A) cases,1 CD71-72(+A) cases,1 IVS-1-1(G→T) cases,1 CD43(G→T) cases,2-29(A→G) cases,2 Codon 36 (-C) cases,the most common mutation was IVS-2-654 (C→T) and CD41-42 (-TCTT),which accounted for 70.95％.A novel β-globin gene mutation CD36 (-C) allele was also detected.The carrier rate of thalassemia in Fujian population is 4.41％.In addition,9 β-thalassemia carriers were found with α-thalassemia mutation.Conclusion The research has revealed the type of gene mutations in α-and β-talassemia in Fujian province.The β-thalassemia mutations in Fujian province are complex,which were also obviously heterogeneous.This will significant value for screening the incidence,provide the valuable information for genetic counseling and prenatal diagnosis.